scholarly journals Gene signature of children with severe respiratory syncytial virus infection

2021 ◽  
Author(s):  
Clyde Dapat ◽  
Satoru Kumaki ◽  
Hiroki Sakurai ◽  
Hidekazu Nishimura ◽  
Hannah Karen Mina Labayo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Blood Coagulation ◽  
Cell Response ◽  
T Cell Response ◽  
Severe Respiratory Syncytial Virus ◽  
Blood Samples ◽  
Cellular Processes ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Background The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection. Methods We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes. Results Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes. Conclusions These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV. Impact Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.

scholarly journals The Human Immune Response to Respiratory Syncytial Virus Infection

2017 ◽  
Vol 30 (2) ◽  
pp. 481-502 ◽  
Author(s):  
Clark D. Russell ◽  
Stefan A. Unger ◽  
Marc Walton ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
T Cell Response ◽  
Rsv Infection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+ T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+ T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

scholarly journals Influence of a Single Viral Epitope on T Cell Response and Disease After Infection of Mice with Respiratory Syncytial Virus

2007 ◽  
Vol 179 (12) ◽  
pp. 8264-8273 ◽  
Author(s):  
Simone Vallbracht ◽  
Birthe Jessen ◽  
Sonja Mrusek ◽  
Anselm Enders ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Viral Epitope ◽  
Syncytial Virus

scholarly journals Regulatory T Cells Promote Early Influx of CD8+ T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities

2009 ◽  
Vol 83 (7) ◽  
pp. 3019-3028 ◽  
Author(s):  
Tracy J. Ruckwardt ◽  
Kathryn L. Bonaparte ◽  
Martha C. Nason ◽  
Barney S. Graham
Keyword(s):  
T Cells ◽  
T Cell ◽  
Treg Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Time Points ◽  
Cell Responses ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT In addition to regulating autoimmunity and antitumor immunity, CD4+ CD25+ FoxP3+ natural regulatory T (Treg) cells are global regulators of adaptive immune responses. Depletion of these cells with the anti-CD25 antibody PC61 prior to primary respiratory syncytial virus (RSV) infection was partial but had several effects on the RSV-specific CD8+ response in a hybrid mouse model. Mediastinal lymph node and spleen epitope-specific CD8+ T-cell responses were enhanced in Treg-cell-depleted mice at all time points following infection, but responses of Treg-cell-depleted lung show a strikingly different pattern than lymphoid organ responses, with an initial delay in the CD8+ T-cell response. The delay in the CD8+ T-cell response correlated with a delay both in the early phase of viral clearance and in illness in Treg-cell-depleted mice compared to isotype-treated controls. The lungs of Treg-cell-depleted mice were shown to have increased lung chemokine and cytokine levels 7 days postinfection despite lower CD8+ T-cell responses. Following the early delay in the lung response, CD8+ T-cell responses at later infection time points were enhanced and increased the severity of illness in depleted mice. Finally, decreasing regulatory T-cell control of the CD8+ T-cell response had a greater effect on response of the dominant Kd-restricted M2 epitope consisting of amino acids 82 to 90 (KdM282-90) than on the subdominant DbM187-195 epitope response, indicating that regulatory T cells modulate immunodominance disparities in epitope-specific CD8+ T-cell responses following primary RSV infection.

scholarly journals Cytotoxic T-cell response to respiratory syncytial virus in mice.

1985 ◽  
Vol 56 (1) ◽  
pp. 55-59 ◽  
Author(s):  
C R Bangham ◽  
M J Cannon ◽  
D T Karzon ◽  
B A Askonas
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Syncytial Virus
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